Academia Sinica

Che Ma

Chi-Huey Wong

Ting-Jen Rachel Cheng

Kuo-I Lin

Cheng-Chi Wang

Hsin-Yu Liao

Han-Yi Huang

Yi-An Ko

Shih-Chi Wang

Juine-Ruey Chen

Chung-Yi Wu

Szu-Wen Wang

Wei-Chieh Cheng

Xiaorui Chen

Yi-Hsuan Chang

Yung-Chieh Tseng

Han-Chung Wu

Wen-Hwa Lee

Jia-Tsrong Jan

Jin-Yuh Shew

Chia-Lin Chen

Wen-Hsin Lee

Chun-Kai Huang

Heng-Hsiung Wu

Yo-Min Liu

The present disclosure provides a glycoengineered SARS-CoV-2 spike protein which is capable of eliciting an enhanced immune response relative to a native spike protein of SARS-CoV-2 and its variants. The glycoengineered spike protein exposes the glycosylation sites and at the same time preserves the tertiary structure of the spike protein. The present disclosure therefore provides improved immunogens, vaccines, and methods for better prevention and treatment of the emerging coronavirus infections.

Coronavirus vaccine

The present disclosure relates to a chimeric influenza virus hemagglutinin (HA) polypeptide, comprising one or more stem domain sequence, each having at least 60% homology with a stem domain consensus sequence of H1 subtype HA (H1 HA) and/or H5 subtype HA (H5 HA), fused with one or more globular head domain sequence, each having at least 60% homology with a globular head domain consensus sequence of H1 subtype HA (H1 HA) or H5 subtype HA (H5 HA).

Chimeric influenza vaccines

The present disclosure relates to an antibody or antigen-binding fragment thereof that specifically binds to a spike protein of SARS-CoV-2. The present disclosure also relates to a pharmaceutical composition, a method for treating and/or preventing diseases and/or disorders caused by a coronavirus in a subject in need thereof, and a method for detecting a coronavirus in a sample.

Antibody specific to spike protein of SARS-CoV-2 and uses thereof

Immunogenic compositions comprising partially glycosylated viral glycoproteins for use as vaccines against viruses are provided. Vaccines formulated using mono-, di-, or tri-glycosylated viral surface glycoproteins and polypeptides provide potent and broad protection against viruses, even across strains. Pharmaceutical compositions comprising monoglycosylated hemagglutinin polypeptides and vaccines generated therefrom and methods of their use for prophylaxis or treatment of viral infections are disclosed. Methods and compositions are disclosed for influenza virus HA, NA and M2, RSV proteins F, G and SH, Dengue virus glycoproteins M or E, hepatitis C virus glycoprotein E1 or E2 and HIV glycoproteins gp120 and gp41.

Methods and compositions for immunization against virus

Methods and compositions for treatment and therapy of cancer are provided. Specifically, antagonists specific for interleukin-17 receptor B (IL-17RB) and its ligand IL-17B are provided. Potent neutralizing antibodies specific for IL-17RB and methods for their manufacture and use are disclosed. The invention also relates to antisense, RNAi and shRNA compositions for the prevention and treatment of cancer, in particular breast cancer and pancreatic cancer.

Isolated antibodies against interleukin-17 receptor B (IL-17RB) for cancer therapy

The present disclosure relates to compositions and methods of use comprising antibodies or binding fragments thereof further comprising universal Fc glycoforms.

Compositions and methods relating to universal glycoforms for enhanced antibody efficacy

The present disclosure relates to glycoproteins, particularly monoclonal antibodies, comprising a glycoengineered Fc region, wherein said Fc region comprises an optimized N-glycan having the structure of Sia(&#x3b1;2-6)GalGlcNAcManGlcNAc. The glycoengineered Fc region binds Fc&#x3b3;RIIA or Fc&#x3b3;RIIIA with a greater affinity, relative to comparable monoclonal antibodies comprising the wild-type Fc region. The monoclonal antibodies of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc&#x3b3;R is desired, e.g., cancer, autoimmune, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Methods for producing virus particles and viral antigens with simplified glycosylation profiles, such as mono-glycosylated forms of HIV, HCV, Dengue virus, West Nile virus and influenza virus. When used as targets for vaccine production, the conserved nature of such sites generate vaccines that are less sensitive to viral mutations. Such methods may include the use of glycosylation inhibitors for production of viruses or viral antigens with simplified glycosylation profiles.

Methods for producing virus particles with simplified glycosylation of surface proteins

The crystal structure at 2.16 &#x212b; resolution of the full-length bacterial bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from, in complex with its inhibitor moenomycin, is provided. The atomic coordinates of the complex as well as the moenomycin binding site are provided. Three dimensional structures of amino acid residues involved in moenomycin binding and transglycosylation activity are identified. Binding site for peptidoglycan synthesis inhibitors comprising inhibitor-binding site comprises amino acid residues from at least one of transglycosylase (TG), UvrB domain 2 homolog (UB2H) and transmembrane (TM) domains of PBP1b are identified at an atomic level of resolution. Methods for rational drug design based on the atomic coordinates are provided. Methods for screening for antibiotics based on anisotropic binding assay and transglycosylase inhibitor assays are provided. Novel antibiotics based on the screening assays of the invention are disclosed.

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Methods for producing virus particles with simplified glycosylation on structural or surface proteins, such as mono-glycosylated forms of influenza A virus, NIBRG-14 (H5N1). When used as targets for vaccine production, the conserved nature of such sites generates vaccines that are less sensitive to viral mutations. Such methods may include the use of glycosylation inhibitors for production of viruses with simplified glycosylation profiles.

Moenomycin inhibits bacterial growth by clocking the transglycosylase activity of class A penicillin-binding proteins (PBPs), which are key enzymes in bacterial cell wall synthesis. The binding affinities of moenomycin A with various truncated PBPs were compared showing that the transmembrane domain is important for moenomycin binding. Full-length class-A PBPs from 16 bacterial species were produced, and their binding activities showed a correlation with the antimicrobial activity of moenomycin againstand. Moreover, a fluorescence anisotropy-based high-throughput assay was developed and used successfully for identification of transglycosylase inhibitors.

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Taipei, Taiwan

Che Ma